Enzalutamide and Niraparib in the Treatment of Metastatic Castrate-Resistant Prostate Cancer (CRPC)
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Combined Targeting of the Androgen Receptor in Metastatic Castrate-Resistant Prostate Cancer With Enzalutamide and the Poly (ADP- Ribose) Polymerase (PARP) Inhibitor Niraparib: Hoosier Cancer Research Network GU14-202|
- Maximum tolerated dose (MTD) for subjects receiving enzalutamide with niraparib without experiencing dose-limiting toxicity(s) (DLT) [ Time Frame: From the start of combination treatment D29 until 30 days after last dose of study treatment per CTCAE v4, assessed up to 52 weeks ] [ Designated as safety issue: Yes ]MTD of niraparib in combination with enzalutamide and MTD for phase II testing.
- Progression-free survival (PFS) with enzalutamide and niraparib combination therapy. [ Time Frame: From the date of enrollment until the criteria for disease progression is met as defined by RECIST 1.1 or death from any cause, whichever occurs first, assessed up to 52 weeks ] [ Designated as safety issue: No ]PFS per RECIST v1.1 for subjects on this combination therapy.
- Objective response (OR) rates for all subjects with confirmed Partial Response (PR) or Complete Response (CR) outcomes, per RECIST v1.1 [ Time Frame: From the date of enrollment until the date of documented disease progression or the date of death from any cause, whichever occurs first, assessed up to 52 weeks ] [ Designated as safety issue: No ]OR outcomes for subjects on this combination therapy, per RECIST v1.1
|Study Start Date:||March 2016|
|Estimated Study Completion Date:||June 2018|
|Estimated Primary Completion Date:||September 2017 (Final data collection date for primary outcome measure)|
Experimental: Experimental Treatment
Subjects will receive enzalutamide 160 mg/day PO in a 28-day lead-in cycle to assess tolerability. If well-tolerated, cycle 1 of combined enzalutamide and niraparib will commence. Enzalutamide will continue at 160 mg PO daily. Niraparib will be administered in three dose-escalation cohorts of 100mg PO, 200mg PO or 300 mg PO daily. Six subjects will be enrolled at each dose level. Each cycle will be 28 days. Combination treatment will continue until documented progression, unmanageable toxicity, or subject or treating investigator decision to discontinue for any reason.
Following completion of 28-day lead-in cycle, enzalutamide 160 mg PO daily will continue to be administered in 28-day cycles until documented progression, unmanageable toxicity, or decision to discontinue for any reason.
Other Name: XtandiDrug: Niraparib
Niraparib will be administered daily in three dose-escalation cohorts of 6 subjects per dose levels of 100mg PO, 200mg PO or 300mg PO in 28-day cycles until documented progression, unmanageable toxicity, or decision to discontinue for any reason.
OUTLINE: This is a multi-center trial.
Each eligible subject will begin treatment with a 28-day enzalutamide 160 mg/day lead-in cycle. If a subject is able to tolerate the lead-in enzalutamide cycle without Grade 2 or Grade 2-4 drug-related toxicity, dose reduction, or missed doses due to toxicity, cycle 1 of combined enzalutamide and niraparib will commence. Enzalutamide will continue at 160 mg daily.
Niraparib will be dosed daily starting at 100mg (dose level 1). Six subjects will be enrolled per dose level. If less than 33% of the subjects experience a dose-limiting toxicity (DLT) at the beginning of cycle 2, then the daily dose of niraparib will escalate to 200mg (dose level 2). If dose level 2 is similarly tolerated, then the daily dose of niraparib escalate to 300mg (dose level 3).
The following required laboratory values must be obtained within 14 days prior to registration for protocol therapy:
- White blood cell count (WBC) ≥ 1500/mm3
- Hemoglobin (Hgb) ≥ 9 g/dL
- Platelets ≥ 150,000/µL
- Absolute neutrophil count (ANC) ≥ 1500/mm3
- Calculated creatinine clearance of ≥ 40 cc/min using the Cockcroft-Gault formula
- Bilirubin ≤ 1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase (AST, SGOT) ≤ 2.5 × ULN
Please refer to this study by its ClinicalTrials.gov identifier: NCT02500901
|United States, Massachusetts|
|Tufts Medical Center|
|Boston, Massachusetts, United States, 02111|
|Study Chair:||Paul Mathew, M.D.||Hoosier Cancer Research Network|